Rotenone is one of the pesticides which thought to have neurotoxic effect that could potentially play a role in the development of Parkinson's disease (PD). Environmental exposure to this pesticide is supposed to be contributed to the increased incidence of PD. This study was done to evaluate rotenone neurotoxicity and the curative role of pramipexole and stem cells therapy in mice. Forty male BALB/c mice were used and divided into 4 equal groups. The control group (G.1) received only carboxymethyl cellulose orally once daily at a volume of 10 ml/kg. The second group was given a daily rotenone  oral dose of 30mg/kg for 28 days. The third group was given oral rotenone (30mg/kg/d for 28 days) then Pramipexole was started from the15th day in a dose of 1 mg/kg/d orally for 14 days with continuing the rotenone course. The fourth group received rotenone (30mg/kg/d orally for 28 days) and in the 15th day 1X105 of Wharton jelly derived mesenchymal stem cells (WJCs) were given intrathecally  and then they completed the rotenone course. At the 23rd day all the animals were subjected to behavioral test for evaluating the degree of PD development. At the end of the 28 days all animals were sacrificed by overdose of phenobarbital and their brain were subjected to immunohistochemical analysis for dopaminergic neurons staining for anti TH antibodies. Behavioural test showed improvement of mice activity in the pramipexole group (18 seconds). Also intrathecal stem cells administration to the mice improved their test performance to reach about 12 seconds. Immunohistochemistry results revealed that the rotenone-induced loss of TH-immunopositive neurons in the SNpc was inhibited by the pramipexole treatment . Intrathecal stem cells administration had also improved the neuronal loss. In conclusion ,the results of this study revealed the neuroprotectant and regenerative capacities of pramipexole and stem cell therapy in improving the rotenone intoxicated mice. So, they could be potential therapeutic approaches in rotenone neurotoxicity specifically toxic parkinsonism.